Idiopathic Membranous Nephropathy (iMN) is an autoimmune disease and a common cause of nephrotic syndrome in adults. Disease evolution is highly variable with spontaneous remission, persistent proteinuria or end-stage kidney disease. In 2009, Beck et al. identified the M-type phospholipase A2 receptor (PLA2R1) as the major podocyte antigen in iMN. The presence of anti-PLA2R1 autoantibodies has been widely confirmed in subsequent studies in 53 to 80% of iMN patients. The pathogenic role of these autoantibodies is not yet proven, but anti-PLA2R1 antibody titers appear to correlate with disease activity in most study populations.
However, individual outcome prediction from anti-PLA2R1 titers is unclear. Indeed, while autoantibodies disappear in most patients during remission, either under symptomatic or immunosuppressive treatments, it may persist during apparent clinical remission under renin-angiotensin system (RAS) blockade. Furthermore, high anti-PLA2R1 antibody titers appear to correlate with subsequent poor renal outcome in most cases but some patients with high autoantibody titers at onset exhibit a sharp decrease of anti-PLA2R1 activity and disease remission.
The treatment of iMN is controversial. KDIGO guidelines (Kidney Disease Improving Global Outcomes) recommend a supportive symptomatic treatment with blockers of the renin angiotensin system and diuretics in all patients with iMN, and immunosuppressive therapy only in case of renal function deterioration or persistent nephrotic syndrome.
Therefore, immunosuppressive treatments are often started only after significant and potentially irreversible complications. On the other hand, an unnecessarily early start of immunosuppression can be futile in patients who might develop remission with symptomatic treatments. Therefore, there is a need for better predictors of the outcome of patients suffering from idiopathic Membranous Nephropathy.
There is thus a long-time felt need for the development of comprehensive, sensitive, and specific methods for the prognosis of idiopathic Membranous Nephropathy. In addition, there is an unfulfilled need for a method for stratifying patients for responsiveness to their treatments in order to provide necessary modifications to ineffective therapeutic regimens.